Abstract Cellular stability is essential for surviving extreme environments. Some cells and organisms can survive in environments even in which their constituent parts are not stable, suggesting that cellular protectants must exist that allow for survival in these contexts. Such protectants have the potential to be utilized for biomedical applications like stabilizing sensitive biological materials, and the mechanisms by which they function are of fundamental biological interest. Aim 1 of this proposal seeks to identify cellular protectants in tardigrades. Tardigrades are invertebrates that can withstand a remarkable variety of environmental stresses including desiccation, freezing, radiation, high pressure, and even the vacuum of space. Previous work has identified a limited number of tardigrade protectant proteins, and remarkably these proteins can confer resistance to desiccation in bacteria and yeast and enhanced radiotolerance in human cells. These studies lay the groundwork to screen for novel tardigrade stress protectant proteins. Protectants of interest identified from this screen will also be expressed in human cell culture in order to study mechanisms by which cellular stability is established, and to identify proteins that are strong candidates for improving stability of biological samples. The second aim of this proposal is to uncover genetic regulation of diapause ? a state of suspended development and increased stress resistance ? in tardigrades. The pathways that control diapause may also regulate production of stress protectants. Therefore, identification of conserved cell signaling pathways required for diapause will inform future studies searching for protectants. Completion of this work will lead to identification of novel protectant molecules and mechanisms of stress resistance that may prove useful for applications like storage of biomaterials.